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Haploidentical stem cell transplantation (SCT) has been generally performed using a T cell depleted (TCD) graft; however, a high rate of nonrelapse mortality (NRM) has been reported, particularly in adult patients. We hypothesized that using a T cell replete (TCR) graft followed by effective posttransplantation immunosuppressive therapy would reduce NRM and improve outcomes. We analyzed 65 consecutive adult patients with hematologic malignancies who received TCR (N = 32) or TCD (N = 33) haploidentical transplants. All patients received a preparative regimen consisting of melphalan, fludarabine, and thiotepa. The TCR group received posttransplantation treatment with cyclophosphamide (Cy), tacrolimus (Tac), and mycophenolate mofetil (MMF). Patients with TCD received antithymocyte globulin followed by infusion of CD34+ selected cells with no posttransplantation immunosuppression. The majority of patients in each group had active disease at the time of transplantation. Outcomes are reported for the TCR and TCD recipients, respectively. Engraftment was achieved in 94% versus 81% (P = NS). NRM at 1 year was 16% versus 42% (P = .02). Actuarial overall survival (OS) and progression-free survival (PFS) rates at 1 year posttransplantation were 64% versus 30% (P = .02) and 50% versus 21% (P = .02). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 20% versus 11% (P = .20), and chronic GVHD (cGVHD) 7% versus 18% (P = .03). Improved reconstitution of T cell subsets and a lower rate of infection were observed in the TCR group. These results indicate that a TCR graft followed by effective control of GVHD posttransplantation may lower NRM and improve survival after haploidentical SCT.